FDA approves flibanserin for hypoactive sexual desire disorder in postmenopausal women

In the alcohol-interaction study, some participants had hypotension or syncope requiring intervention, such as being placed supine or in Trendelenburg position, when they took flibanserin with the equivalent of as little as two alcoholic drinks for someone weighing 70 kg (e.g., two 5-oz glasses of wine containing 12% alcohol).

These participants had systolic and diastolic blood-pressure reductions of 28 to 54 mm Hg and 24 to 46 mm Hg, respectively.

• The prescribing guidelines emphasize cautious use in women on other psychotropic drugs.
• Flibanserin's approval was driven by a need for female-specific sexual health medications.
• Its mechanism involves serotonergic pathways impacting sexual response.
• The drug is typically part of a broader therapy including counseling or therapy.
• Studies indicate a small but statistically significant benefit for some women.
• It is important to rule out other medical or psychological causes before use.
• Flibanserin is contraindicated with certain medications, such as CYP3A4 inhibitors.
• Side effect management includes monitoring blood pressure and mental status.
• The medication's role is to improve quality of life by addressing sexual desire challenges.

The study did not definitively delineate the risk in premenopausal women who take flibanserin at bedtime because 23 of the 25 participants were men, flibanserin was administered in the morning, and alcohol was consumed rapidly (within 10 minutes). In the phase 3 trials, in which alcohol consumption was not restricted and flibanserin was taken at bedtime, the incidence of syncope was 0.4% with flibanserin and 0.2% with placebo.

Problems and controversies

They can help make sure Addyi (flibanserin) is safe for you to take. Follow any directions they give you if you need to switch or stop medications to lower the risk of dangerous drug interactions. Addyi (flibanserin) can cause dangerously low blood pressure and lead to fainting in people with liver problems. Because of this risk, people with liver problems can't take this medication. If you have liver problems, tell your prescriber before you start taking Addyi (flibanserin).

Patient resources

Risk factors: Taking Addyi (flibanserin) during the day Drinking alcohol Taking other medications that can cause sleepiness Taking medications, supplements, or foods that interact with Addyi (flibanserin) Addyi (flibanserin) can make you feel sleepy, tired, and less alert. These side effects can affect your ability to think and focus well. Your risk is higher if you take Addyi (flibanserin) during the day, with alcohol, or with other medications that have similar side effects. Take Addyi (flibanserin) only libido booster for woman at bedtime to prevent these side effects. Also avoid driving a car or doing other activities that need your attention until at least 6 hours after you take Addyi (flibanserin) and until you know how the medication affects you. Although these data appear more reassuring, the extent of alcohol use during these trials was not recorded.

Because of residual concerns about the benefit–risk profile, the FDA rejected flibanserin again and requested additional data, including a study to ensure that CNS depression would not affect next-day driving performance.

• Summary: A daily, non-hormonal pill for premenopausal women with HSDD.
• Key benefit: Modest increase in sexual desire and satisfying events for some.
• Key risk: Potentially severe interactions with alcohol and many medications.
• Management: Strict adherence to REMS, bedtime dosing, and no alcohol.
• Patient profile: Premenopausal woman with distress from low desire, otherwise healthy.
• Provider role: Certify, counsel, monitor, and manage expectations.
• Place in therapy: One option among a comprehensive approach to sexual health.
• Public health impact: Highlighted need for and challenges in female sexual medicine.
• Future: Continued evaluation of real-world outcomes and safety profile.

This rejection prompted allegations of gender bias at the FDA, based on erroneous claims that it had approved more than 20 drugs for male sexual dysfunction and none for women.

What does it ‘treat’?

Don't drink any alcohol after you take Addyi (flibanserin); wait until the next day. Taking Addyi (flibanserin) and drinking alcohol too close together can put you at greater risk for low blood pressure and fainting. Avoid eating grapefruit or drinking grapefruit juice at any time while you're taking Addyi (flibanserin). Grapefruit can raise your risk of side effects while you're taking this medication. Tell your care team and pharmacist about all the medications, supplements, or foods you take or planning to take.

Who should not use Addyi?

Certain medications, herbal supplements, and foods can raise your risk of side effects, such as sleepiness, low blood pressure, and fainting, while you're taking Addyi (flibanserin). If you miss a dose of Addyi (flibanserin) at bedtime, wait until the next night to take your next dose. Don't double up on doses to make up for a missed dose because this can raise your risk for side effects. Addyi (flibanserin) can cause some serious health issues. This risk may be even higher for certain groups. (Those making such assertions included Even the Score, an advocacy campaign partly funded by Sprout Pharmaceuticals, flibanserin's sponsor after Boehringer Ingelheim sold the rights to the drug.) The FDA rejected these claims and clarified what products had been approved (see Table 2).

Addyi is the #1 Prescribed Treatment by doctors for HSDD.1

Assessing flibanserin has proven challenging; the drug has been reviewed three times by the FDA and discussed twice at public advisory committee meetings. The first advisory committee, convened in 2010, unanimously recommended against approval.2 In the two phase 3 trials, one primary end point, satisfying sexual events, was achieved, but the other, daily sexual desire, was not. Although the trials showed an effect on sexual desire over the previous 4 weeks as recalled by participants — assessed with the Female Sexual Function Index (FSFI) — the committee believed that an effect on daily recall of sexual desire was preferable and thought that results on the FSFI, a secondary end point, should not override the failure to achieve a primary end point. The committee also expressed concern about adverse effects such as somnolence fildena 120 and drug interactions. The FDA rejected the application and requested additional studies, including a new phase 3 trial, an alcohol-interaction study, and drug–drug interaction studies. After completing the additional studies, Sprout submitted flibanserin for a third review.

In case of emergency/overdose

If this worries you, talk to your doctor or pharmacist fildena 200 mg about other options. Taking Addyi (flibanserin) and drinking alcohol too close together can put you at risk for dangerously low blood pressure, dizziness, and fainting. To prevent accidental injury from these side effects, wait at least 2 hours after drinking 1 or 2 standard alcoholic drinks before you take Addyi (flibanserin) at bedtime. Skip your dose for the night if you've had 3 or more alcoholic drinks. Don't drink any alcohol after you take Addyi (flibanserin) until the next day.

Dosage Modifications

Risk factors: Taking medications, herbal supplements, or foods that interact with Addyi (flibanserin) Addyi (flibanserin) can interact with certain medications, herbal supplements, and foods. These interactions can make your blood pressure drop to dangerous levels and lead to fainting. Some common medications and foods that interact with Addyi (flibanserin) include ciprofloxacin (Cipro), fluconazole (Diflucan), birth control pills, and grapefruit. Ask your prescriber or pharmacist for a complete list of medications, supplements, and foods to avoid. Tell your care team all the other medications and herbal supplements you're taking. The FDA convened another advisory committee to obtain advice on the benefit–risk profile, given the new data.

IN THEIR WORDS

Boehringer Ingelheim, the original applicant, completed a new phase 3 trial with the primary end points of satisfying sexual events and sexual desire as assessed by the FSFI; a secondary end point was reduction of distress related to low sexual desire. All three were achieved, and results were consistent with previous findings. However, treatment effects in all three phase 3 trials were small (see Table 1). Major safety concerns regarding flibanserin include risks of hypotension, syncope, and central nervous system (CNS) depression (e.g., somnolence). These risks increase when the drug is taken during the day, with concomitant use of any of the numerous moderate or strong cytochrome P-450 3A4 (CYP3A4) inhibitors such as some of the antiretroviral drugs, antihypertensive drugs, antibiotics, and fluconazole (which increase systemic exposure to flibanserin by a factor of 4.5 to 7), and with alcohol use. By a vote of 18 to 6, the committee recommended approval, though some members said it was a difficult decision.

In general, those recommending approval acknowledged the small treatment effects and substantial safety concerns but considered the unmet medical need. All votes for approval were contingent on the inclusion of risk-mitigation strategies beyond labeling.

After the advisory committee meeting, the FDA received requests to reject flibanserin again, citing insufficient alcohol-interaction data in women, the infeasibility of abstaining indefinitely from alcohol, drug–drug interactions, the importance of nonpharmacologic approaches to HSDD, concerns about “medicalizing” low sexual desire, and the change from HSDD to “female sexual interest/arousal disorder” (FSIAD) in the newest edition of the Diagnostic and Statistical Manual of Mental Disorders.

Microcircuits and Sexual Interest and Desire

It's possible to have an allergic reaction to Addyi (flibanserin). Stop taking the medication and call for medical help right away if you notice any swelling of your face, lips, or mouth; itchiness; hives; or trouble breathing. The typical dose is 100 mg by mouth once a day at bedtime. Contraindications are specific health conditions or situations in which a person should not take a medication due to safety concerns. If you have any of the following conditions or if any of the following apply to you, let your healthcare provider know because Addyi (flibanserin) will not be safe for you to take.

CNS Activity

Take certain medications that interact with Addyi (flibanserin) and put you at risk for low blood pressure and fainting N Engl J Med 2016;374:101-104 Was the Food and Drug Administration (FDA) approval of flibanserin (Addyi) for treatment of hypoactive sexual desire disorder (HSDD) in premenopausal women long overdue? In the face of divergent views, we at the FDA think it's important to clarify why flibanserin was approved after being rejected twice. HSDD is characterized by reduced sexual fantasies and desire for sexual activity that causes marked distress or interpersonal difficulty and is not accounted for by coexisting conditions, use of medications, or relationship problems. At a 2014 meeting, the FDA heard from some women about the condition's effects on their sense of identity, emotional well-being, and relationships.1 Although nonpharmacologic approaches to HSDD are important, we recognized that some women could benefit from drug therapy. Such treatments must meet the statutory standard for demonstration of effectiveness (substantial evidence from adequate, well-controlled trials) and have favorable benefit–risk profiles. Patients with HSDD generally meet the criteria for FSIAD if they've had symptoms for at least 6 months and are typically unreceptive to a partner's attempts to initiate sexual activity, but whereas HSDD requires distress caused by low sexual desire, the definition of FSIAD includes distress caused by low sexual desire, low sexual arousal, or both.